Sexually transmitted diseases (STDs) in the world.

Sexually transmitted diseases (STDs) represent a major public health problem in the world and the advent and increase of human immunodeficiency virus infection during the last decade has highlighted the importance of infections spread by the sexual route. The World Health Organization estimates that the global incidence in 1995 of new cases of selected curable STDs, which are gonorrhea, chlamydial infection, syphilis and trichomoniasis, was 333 million. Control programs for STDs must prevent the acquisition of STDs, their complications and sequelae and interrupt and reduce transmission.     

Estimation of the basic reproduction number of BSE: the intensity of transmission in British cattle

The basic reproduction number, R0, of an infectious agent is a key factor determining the rate of spread and the proportion of the host population affected. We formulate a general mathematical framework to describe the transmission dynamics of long incubation period diseases with complex pathogenesis. This is used to derive expressions for R0 of bovine spongiform encephalopathy (BSE) in British cattle, and back-calculation methods are used to estimate R0 throughout the time-course of the BSE epidemic. We show that the 1988 meat and bonemeal ban was effective in rapidly reducing R0 below 1, and demonstrate that this indicates that BSE will be unable to become endemic in the UK cattle population even when case clustering is taken into account. The analysis provides some insight into absolute infectiousness for bovine-to-bovine transmission, indicating maximally infectious animals may have infected up to 400 animals each. The relationship between R0 and the early stages of the BSE epidemic and the requirements for additional research are also discussed.     

Stage-structured transmission of phocine distemper virus in the Dutch 2002 outbreak

Heterogeneities in transmission among hosts can be very important in shaping infectious disease dynamics. In mammals with strong social organization, such heterogeneities are often structured by functional stage: juveniles, subadults and adults. We investigate the importance of such stage-related heterogeneities in shaping the 2002 phocine distemper virus (PDV) outbreak in the Dutch Wadden Sea, when more than 40 per cent of the harbour seals were killed. We do this by comparing the statistical fit of a hierarchy of models with varying transmission complexity: homogeneous versus heterogeneous mixing and density- versus frequency-dependent transmission. We use the stranding data as a proxy for incidence and use Poisson likelihoods to estimate the ‘who acquires infection from whom’ (WAIFW) matrix. Statistically, the model with strong heterogeneous mixing and density-dependent transmission was found to best describe the transmission dynamics. However, patterns of incidence support a model of frequency-dependent transmission among adults and juveniles. Based on the maximum-likelihood WAIFW matrix estimates, we use the next-generation formalism to calculate an R₀ between 2 and 2.5 for the Dutch 2002 PDV epidemic.     

兽类在流行病学中的作用

在各种疾病中,有些是与人类和动物都有关系的,如鼠疫、布鲁氏菌病、马堡热、拉萨热等,称为人兽共患疾病(Anthropozoonoses)。这些疾病的病原体既能传染给人又能传染给动物,造成人或兽类的疾病流行。在医学上也叫动物性病。据Hubbert(1975)等的统计有162种;约占人类传染病的1/5左右(耿贯一,1980)动物性病,实质是自然界中一个生物学现象和生态学问题。是生物间在一定地理景观(Landscape)中通过“食物链”联系演化成相互依存、相互制约、相互适应,并借以维持其种系延续的生物群落(Biocenosis或Community)的关系(1964)     

Theory versus data: how to calculate R0?

To predict the potential severity of outbreaks of infectious diseases such as SARS, HIV, TB and smallpox, a summary parameter, the basic reproduction number R(0), is generally calculated from a population-level model. R(0) specifies the average number of secondary infections caused by one infected individual during his/her entire infectious period at the start of an outbreak. R(0) is used to assess the severity of the outbreak, as well as the strength of the medical and/or behavioral interventions necessary for control. Conventionally, it is assumed that if R(0)>1 the outbreak generates an epidemic, and if R(0)<1 the outbreak becomes extinct. Here, we use computational and analytical methods to calculate the average number of secondary infections and to show that it does not necessarily represent an epidemic threshold parameter (as it has been generally assumed). Previously we have constructed a new type of individual-level model (ILM) and linked it with a population-level model. Our ILM generates the same temporal incidence and prevalence patterns as the population-level model; we use our ILM to directly calculate the average number of secondary infections (i.e., R(0)). Surprisingly, we find that this value of R(0) calculated from the ILM is very different from the epidemic threshold calculated from the population-level model. This occurs because many different individual-level processes can generate the same incidence and prevalence patterns. We show that obtaining R(0) from empirical contact tracing data collected by epidemiologists and using this R(0) as a threshold parameter for a population-level model could produce extremely misleading estimates of the infectiousness of the pathogen, the severity of an outbreak, and the strength of the medical and/or behavioral interventions necessary for control.     

Seasonal infectious disease epidemiology

Seasonal change in the incidence of infectious diseases is a common phenomenon in both temperate and tropical climates. However, the mechanisms responsible for seasonal disease incidence, and the epidemiological consequences of seasonality, are poorly understood with rare exception. Standard epidemiological theory and concepts such as the basic reproductive number R0 no longer apply, and the implications for interventions that themselves may be periodic, such as pulse vaccination, have not been formally examined. This paper examines the causes and consequences of seasonality, and in so doing derives several new results concerning vaccination strategy and the interpretation of disease outbreak data. It begins with a brief review of published scientific studies in support of different causes of seasonality in infectious diseases of humans, identifying four principal mechanisms and their association with different routes of transmission. It then describes the consequences of seasonality for R0, disease outbreaks, endemic dynamics and persistence. Finally, a mathematical analysis of routine and pulse vaccination programmes for seasonal infections is presented. The synthesis of seasonal infectious disease epidemiology attempted by this paper highlights the need for further empirical and theoretical work.     

Demonstrating frequency-dependent transmission of sarcoptic mange in red foxes

Understanding the relationship between disease transmission and host density is essential for predicting disease spread and control. Using long-term data on sarcoptic mange in a red fox Vulpes vulpes population, we tested long-held assumptions of density- and frequency-dependent direct disease transmission. We also assessed the role of indirect transmission. Contrary to assumptions typical of epidemiological models, mange dynamics are better explained by frequency-dependent disease transmission than by density-dependent transmission in this canid. We found no support for indirect transmission. We present the first estimates of R₀ and age-specific transmission coefficients for mange in foxes. These parameters are important for managing this poorly understood but highly contagious and economically damaging disease.     

The evolution of virulence in pathogens with frequency-dependent transmission

Frequency-dependent transmission is an important feature of diseases that are sexually transmitted or transmitted by a vector that actively searches for hosts. Here I describe the evolution of virulence in pathogens that have frequency-dependent transmission. I consider two components of virulence--an increase in host mortality due to infection, as is classically described, and a decrease in host fecundity due to infection, because frequency dependence is common among diseases that fully or partially sterilize their hosts. Theoretical predictions pertaining to host-pathogen numerical dynamics can be quite different between pathogens with frequency-dependent transmission and those with density-dependent transmission. In contrast, this study suggests that the principles governing the evolution of virulence that have been established in the context of density-dependent pathogens may also apply (qualitatively) to frequency-dependent pathogens. I examine the evolutionary trajectories of the mortality and sterility components of virulence as well as the role of spatial population structure in the evolution of the sterility component of virulence.     

How often is genital yeast infection sexually transmitted?

We analysed data from a computer-based bank of clinical records of patients seen in a clinic for sexually transmitted diseases over a three-year period to investigate the association between genital yeast infections and sexually transmitted diseases (STDs). We classified STDs as primary and secondary syphilis; gonorrhoea; lymphogranuloma venereum; trichomoniasis; scabies; pediculosis; genital herpes; warts; and molluscum contagiosum. Of a total of 2984 disease episodes among women, 1054 (35-3%) included yeast infections, whereas only 382 (6-9%) of 5501 episodes in heterosexual men were associated with yeast infections, We found a significant association between yeast infection and STD and non-specific genital infection (non-specific urethritis (NSU) and procitis in men, and female contacts of men with NSU), which suggested that yeast infection was sexually acquired in 414 out of 1054 disease episodes in women (39%) and 110 out of 382 episodes in heterosexual men (29%). We conclude that sexually active patients with genital yeast infections should be screened for other STDs particularly non-specific genital infection.     

Mathematical analysis of a cholera model with public health interventions

Cholera, an acute gastro-intestinal infection and a waterborne disease continues to emerge in developing countries and remains an important global health challenge. We formulate a mathematical model that captures some essential dynamics of cholera transmission to study the impact of public health educational campaigns, vaccination and treatment as control strategies in curtailing the disease. The education-induced, vaccination-induced and treatment-induced reproductive numbers R(E), R(V), R(T) respectively and the combined reproductive number R(C) are compared with the basic reproduction number R(0) to assess the possible community benefits of these control measures. A Lyapunov functional approach is also used to analyse the stability of the equilibrium points. We perform sensitivity analysis on the key parameters that drive the disease dynamics in order to determine their relative importance to disease transmission and prevalence. Graphical representations are provided to qualitatively support the analytical results.     

Global dynamics of a staged-progression model with amelioration for infectious diseases

We analyze the global dynamics of a mathematical model for infectious diseases that progress through distinct stages within infected hosts with possibility of amelioration. An example of such diseases is HIV/AIDS that progresses through several stages with varying degrees of infectivity; amelioration can result from a host's immune action or more commonly from antiretroviral therapies, such as highly active antiretroviral therapy. For a general n-stage model with constant recruitment and bilinear incidence that incorporates amelioration, we prove that the global dynamics are completely determined by the basic reproduction number R(0). If R(0)≤1, then the disease-free equilibrium P(0) is globally asymptotically stable, and the disease always dies out. If R(0)>1, P(0) is unstable, a unique endemic equilibrium P* is globally asymptotically stable, and the disease persists at the endemic equilibrium. Impacts of amelioration on the basic reproduction number are also investigated.     

Transmission and dynamics of tuberculosis on generalized households

Tuberculosis (TB) transmission is enhanced by systematic exposure to an infectious individual. This enhancement usually takes place at either the home, workplace, and/or school (generalized household). Typical epidemiological models do not incorporate the impact of generalized households on the study of disease dynamics. Models that incorporate cluster (generalized household) effects and focus on their impact on TB's transmission dynamics are developed. Detailed models that consider the effect of casual infections, that is, those generated outside a cluster, are also presented. We find expressions for the Basic Reproductive Number as a function of cluster size. The formula for R0 separates the contributions of cluster and casual infections in the generation of secondary TB infections. Relationships between cluster and classical epidemic models are discussed as well as the concept of critical cluster size.     

Sexually transmitted diseases of insects: distribution, evolution, ecology and host behaviour

Sexually transmitted diseases (STDs) of insects are known from the mites, nematodes, fungi, protists and viruses. In total 73 species of parasite and pathogen from approximately 182 species of host have been reported. Whereas nearly all vertebrate STDs are viruses or bacteria, the majority of insect STDs are multicellular ectoparasites, protistans or fungi. Insect STDs display a range of transmission modes, with 'pure' sexual transmission only described from ectoparasites, all of which are mites, fungi or nematodes, whereas the microparasitic endo-parasites tend to show vertical as well as sexual transmission. The distribution of STDs within taxa of insect hosts appears to be related to the life histories of the hosts. In particular, STDs will not be able to persist if host adult generations do not overlap unless they are also transmitted by some alternative route. This explains the observation that the Coleoptera seem to suffer from more STDs than other insect orders, since they tend to diapause as adults and are therefore more likely to have overlapping generations of adults in temperate regions. STDs of insects are often highly pathogenic, and are frequently responsible for sterilizing their hosts, a feature which is also found in mammalian STDs. This, combined with high prevalences indicates that STDs can be important in the evolution and ecology of their hosts. Although attempts to demonstrate mate choice for uninfected partners have so far failed it is likely that STDs have other effects on host mating behaviour, and there is evidence from a few systems that they might manipulate their hosts to cause them to mate more frequently. STDs may also play a part in sexual conflict, with males in some systems possibly gaining a selective advantage from transmitting certain STDs to females. STDs may well be important factors in host population dynamics, and some have the potential to be useful biological control agents, but empirical studies on these subjects are lacking.     

A Contact-Network-Based Formulation of a Preferential Mixing Model

Heterogeneity in the number of potentially infectious contacts and connectivity correlations (“like attaches to like” i.e., assortatively mixed or “opposites attract” i.e., disassortatively mixed) have important implications for the value of the basic reproduction ratio R ₀ and final epidemic size. In this paper, we present a contact-network-based derivation of a simple differential equation model that accounts for preferential mixing based on the number of contacts. We show that results based on this model are in good qualitative agreement with results obtained from preferential mixing models used in the context of sexually transmitted diseases (STDs). This simple model can accommodate any mixing pattern ranging from completely disassortative to completely assortative and allows the derivation of a series of analytical results.     

Wildlife disease elimination and density dependence

Disease control by managers is a crucial response to emerging wildlife epidemics, yet the means of control may be limited by the method of disease transmission. In particular, it is widely held that population reduction, while effective for controlling diseases that are subject to density-dependent (DD) transmission, is ineffective for controlling diseases that are subject to frequency-dependent (FD) transmission. We investigate control for horizontally transmitted diseases with FD transmission where the control is via culling or harvest that is non-selective with respect to infection and the population can compensate through DD recruitment or survival. Using a mathematical model, we show that culling or harvesting can eradicate the disease, even when transmission dynamics are FD. Eradication can be achieved under FD transmission when DD birth or recruitment induces compensatory growth of new, healthy individuals, which has the net effect of reducing disease prevalence by dilution. We also show that if harvest is used simultaneously with vaccination, and there is high enough transmission coefficient, application of both controls may be less efficient than vaccination alone. We illustrate the effects of these control approaches on disease prevalence for chronic wasting disease in deer where the disease is transmitted directly among deer and through the environment.     

Local transmission processes and disease-driven host extinctions

Classic infectious disease theory assumes that transmission depends on either the global density of the parasite (for directly transmitted diseases) or its global frequency (for sexually transmitted diseases). One important implication of this dichotomy is that parasite-driven host extinction is only predicted under frequency-dependent transmission. However, transmission is fundamentally a local process between individuals that is determined by their and/or their vector’s behaviour. We examine the implications of local transmission processes to the likelihood of disease-driven host extinction. Local density-dependent transmission can lead to parasite-driven extinction, but extinction is more likely under local frequency-dependent transmission and much more likely when there is active local searching behaviour. Density-dependent directly transmitted diseases spread locally can therefore lead to deterministic host extinction, but locally frequency-dependent passive vector-borne diseases are more likely to cause extinctions. However, it is active searching behaviour either by a vector or between sexual partners that is most likely to cause the host to go extinct. Our work emphasises that local processes are essential in determining parasite-driven extinctions, and the role of parasites in the extinction of rare species may have been underplayed due to the classic assumption of global density-dependent transmission.     

Symmetric competition as a general model for single-species adaptive dynamics

Adaptive dynamics is a widely used framework for modeling long-term evolution of continuous phenotypes. It is based on invasion fitness functions, which determine selection gradients and the canonical equation of adaptive dynamics. Even though the derivation of the adaptive dynamics from a given invasion fitness function is general and model-independent, the derivation of the invasion fitness function itself requires specification of an underlying ecological model. Therefore, evolutionary insights gained from adaptive dynamics models are generally model-dependent. Logistic models for symmetric, frequency-dependent competition are widely used in this context. Such models have the property that the selection gradients derived from them are gradients of scalar functions, which reflects a certain gradient property of the corresponding invasion fitness function. We show that any adaptive dynamics model that is based on an invasion fitness functions with this gradient property can be transformed into a generalized symmetric competition model. This provides a precise delineation of the generality of results derived from competition models. Roughly speaking, to understand the adaptive dynamics of the class of models satisfying a certain gradient condition, one only needs a complete understanding of the adaptive dynamics of symmetric, frequency-dependent competition. We show how this result can be applied to number of basic issues in evolutionary theory.     

Sexually transmitted disease and the evolution of mating systems

Sexually transmitted diseases (STDs) have been shown to increase the costs of multiple mating and therefore favor relatively monogamous mating strategies. We examine another way in which STDs can influence mating systems in species in which female choice is important. Because more popular males are more likely to become infected, STDs can counteract any selective pressure that generates strong mating skews. We build two models to investigate female mate choice when the sexual behavior of females determines the prevalence of infection in the population. The first model has no explicit social structure. The second model considers the spatial distribution of matings under social monogamy, when females mated to unattractive males seek extrapair fertilizations from attractive males. In both cases, the STD has the potential to drastically reduce the mating skew. However, this reduction does not always happen. If the per contact transmission probability is low, the disease dies out and is of no consequence. In contrast, if the transmission probability is very high, males are likely to be infected regardless of their attractiveness, and mating with the most attractive males imposes again no extra cost for the female. We also show that optimal female responses to the risk of STDs can buffer the prevalence of infection to remain constant, or even decrease, with increasing per contact transmission probabilities. In all cases considered, the feedback between mate choice strategies and STD prevalence creates frequency-dependent fitness benefits for the two alternative female phenotypes considered (choosy vs. randomly mating females or faithful vs. unfaithful females). This maintains mixed evolutionarily stable strategies or polymorphisms in female behavior. In this way, a sexually transmitted disease can stabilize the populationwide proportion of females that mate with the most attractive males or that seek extrapair copulations.     

Sexually transmitted disease epidemics in a natural insect population

1. The epidemiology of sexually transmitted diseases (STDs) in human and domesticated populations is well documented. However, there has been less study of STDs in natural populations. 2. We investigated STD dynamics in the model system involving a host from the most speciose group of animals: the insects. We investigated temporal variation in the prevalence of the sexually transmitted mite Coccipolipus hippodamiae on its ladybird host, Adalia bipunctata. 3. Field surveys over two seasons showed a repeated pattern of a profound epidemic in the overwintered cohort and a later prevalence decline. 4. In order to understand the key factors in the dynamics of this system we studied the phenology of the host and simulated parasite dynamics in the overwintered cohort using a model with within-sex homogeneity in mating rate and field-measured parameter values. The similarity of natural and simulation prevalence levels allowed us to carry out sensitivity analysis and hence to identify the key determinants of the dynamics. 5. The observed pattern of periodic extreme prevalence combined with system persistence probably results from time lags in host recruitment and widespread promiscuity. 6. Our findings improve our understanding of STDs in natural populations and illustrate the importance of examining seasonality and time delays in population dynamics in order to fully understand the characteristics of natural populations and their parasites.     

Likelihood-based inference for stochastic models of sexual network formation

Sexually-transmitted diseases (STDs) constitute a major public health concern. Mathematical models for the transmission dynamics of STDs indicate that heterogeneity in sexual activity level allow them to persist even when the typical behavior of the population would not support endemicity. This insight focuses attention on the distribution of sexual activity level in a population. In this paper, we develop several stochastic process models for the formation of sexual partnership networks. Using likelihood-based model selection procedures, we assess the fit of the different models to three large distributions of sexual partner counts: (1) Rakai, Uganda, (2) Sweden, and (3) the USA. Five of the six single-sex networks were fit best by the negative binomial model. The American women's network was best fit by a power-law model, the Yule. For most networks, several competing models fit approximately equally well. These results suggest three conclusions: (1) no single unitary process clearly underlies the formation of these sexual networks, (2) behavioral heterogeneity plays an essential role in network structure, (3) substantial model uncertainty exists for sexual network degree distributions. Behavioral research focused on the mechanisms of partnership formation will play an essential role in specifying the best model for empirical degree distributions. We discuss the limitations of inferences from such data, and the utility of degree-based epidemiological models more generally.